A numerical simulation study was conducted to investigate the dynamic response and failure behavior of thermoplastic fiber-metal laminates (TFMLs) under confined explosion conditions. To simulate the response of TFMLs to high-impact loads, a subroutine was developed incorporating the strain rate effect. In addition, a surrogate model for predicting the dynamic response of TFMLs was established by employing parametric modeling combined with Gaussian process regression analysis. Bayesian optimization of the thickness ratios for each layer group of the laminates was performed, using lightweight and protective performance as the comprehensive evaluation indices. The results indicate that incorporating the strain rate effect facilitates reliable characterization of both overall deformation and internal damage of TFMLs. The deviation of peak deflection between the numerically calculated value and experimental results is approximately 3 %, while the error for residual deflection is <10 %. A comparative analysis shows that the strain rate effect has significant influence both on the overall deformation and internal fiber damage of the blast loaded TFMLs. Furthermore, optimizing the thickness of each stack achieved an 11.9 % reduction in areal density and a 1.6 % reduction in residual deflection compared to those of the original design scheme. Increasing the metal thickness ratios on the front and rear faces of the laminated structure was shown to significantly enhance its protective performance. This research will contribute to advancing methodologies for analyzing the dynamic response and optimizing the structural design of TFMLs.